Department of Pediatrics, Harbor-UCLA Medical Center and The Lundquist Institute for Biomedical Innovation, Torrance, CA, USA.
SIDMAP, LLC, Los Angeles, CA, USA.
Cancer Control. 2021 Jan-Dec;28:1073274821999655. doi: 10.1177/1073274821999655.
The effects of deuterium-depleted water (DDW) containing deuterium (D) at a concentration of 25 parts per million (ppm), 50 ppm, 105 ppm and the control at 150 ppm were monitored in MIA-PaCa-2 pancreatic cancer cells by the real-time cell impedance detection xCELLigence method. The data revealed that lower deuterium concentrations corresponded to lower MiA PaCa-2 growth rate. Nuclear membrane turnover and nucleic acid synthesis rate at different D-concentrations were determined by targeted [1,2-C]-D-glucose fate associations. The data showed severely decreased oxidative pentose cycling, RNA ribose C labeling from [1,2-C]-D-glucose and nuclear membrane lignoceric (C24:0) acid turnover. Here, we treated advanced pancreatic cancer patients with DDW as an extra-mitochondrial deuterium-depleting strategy and evaluated overall patient survival. Eighty-six (36 male and 50 female) pancreatic adenocarcinoma patients were treated with conventional chemotherapy and natural water (control, 30 patients) or 85 ppm DDW (56 patients), which was gradually decreased to preparations with 65 ppm and 45 ppm deuterium content for each 1 to 3 months treatment period. Patient survival curves were calculated by the Kaplan-Meier method and Pearson correlation was taken between medial survival time (MST) and DDW treatment in pancreatic cancer patients. The MST for patients consuming DDW treatment (n = 56) was 19.6 months in comparison with the 6.36 months' MST achieved with chemotherapy alone (n = 30). There was a strong, statistically significant Pearson correlation (r = 0.504, p < 0.001) between survival time and length and frequency of DDW treatment.
采用实时细胞阻抗检测 xCELLigence 方法,监测含氘(D)浓度为 25ppm、50ppm、105ppm 和对照(150ppm)的重水(DDW)对胰腺癌细胞 MIA-PaCa-2 的影响。数据显示,较低的氘浓度对应较低的 MiA PaCa-2 生长速度。通过靶向[1,2-C]-D-葡萄糖命运关联,确定了不同 D 浓度下核膜周转率和核酸合成率。结果显示,氧化戊糖循环、来自[1,2-C]-D-葡萄糖的 RNA 核糖 C 标记和核膜木质酸(C24:0)周转率严重下降。在这里,我们将 DDW 作为一种额外的线粒体去氘策略用于治疗晚期胰腺癌患者,并评估了患者的总生存率。86 名(36 名男性和 50 名女性)胰腺腺癌患者接受常规化疗和天然水(对照,30 名患者)或 85ppm DDW(56 名患者)治疗,治疗期间每个月将 DDW 中的氘含量逐渐降低至 65ppm 和 45ppm。采用 Kaplan-Meier 法计算患者生存曲线,并对胰腺癌患者的中位生存时间(MST)与 DDW 治疗之间进行 Pearson 相关性分析。接受 DDW 治疗的患者(n=56)的 MST 为 19.6 个月,而单独接受化疗的患者(n=30)的 MST 为 6.36 个月。生存时间与 DDW 治疗的长度和频率之间存在强烈的、统计学显著的 Pearson 相关性(r=0.504,p<0.001)。